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Advances In Experimental Medicine and Biology 1990; 267:327-44

HOT SPOT’

TRIPAS : A TRIAPPLICATOR SYSTEM WITH RELOCATABLE

AT TISSUE DEPTH

Haim I. Bicher, Samuel A. Afuwape, Ralph S. Wolfstein, Duane F. Bruley, and Kenneth Reesman

Valley Cancer Institute,!Panorama City, CA 91402

ABSTRACT

Solving the pr of the clinica!

mathematical predi ction model. The model should include the

medium constituti positioning of treatment p!annin set-up. We

subtended by an eq uilateral triangle in order to target and

oblem of heat focusing and standardization application of hyperthermia requires a

ve parameter, and be able to predict

the microwave applicators to

optimize

g and provide for reproducible treatment pre sent a configuration of 3 applicators

relocate a ’hot sp

ot’ for improved treatment of deep tumors.

A simple geometri c analysis is illustrated. The microwave

beam absorption pr ofile~ from the three power sources~ was

obtained from pha pattern for the mathematical model

of the beams in th e medium.

ntom studies depicting the radiative heat triapplicator system (TRIPAS). A complex was developed to demonstrate interaction

It was

observed empirically that

under

coherent

propagation in the near field electromagnetic (EM) waves tend to add at the center, while varying the propagation axial focal length caused a relocation of the summing focal points.

Mathematical prediction correlated very well with the phantom studies. SAR values above 100 W/kg were achieved at 12.5 cm phantom depth, creating a relocatable ’hot spot’ at the concentric loci of the 3 air cooled horn microwave applicators operating at 300 MHz.

This Project is supported in part by a computational from !BM LASC, Los Angeles Ca, USA!.

Consensus on Hyperthermia for the 1990s Edited by H. I. Bicher et al. Plenum Press, New York, 1990

grant

327

INTRODUCTION

been

extensively analyzed Johnson et al. 1985,

some devices are available for regional deep hyperthermia applied to different areas of the body, the probem of insufficient energy penetration persists. Heretofore this

by several authors (Andersen 1984, and Turner and Kumar 1982). Although

The

oroblem of

microwave deep heating

has

has been only partially solved by multiple phased array applicator configurations (Bach Anderson 1984, Gee et a! !98~, Samulski et al. 1987 and Sato et al. !986). The

rationale behind these technioues is the in-ohase, coherent

several

addition

of electromagnetic (EMI energy from

strateaically located sources. The selection of a source freauency lower than 300 MHz theoretically enhances deeper penetration while oaradoxically limiting localization of the energy to a defined tumor volume. In prior publications ( Bicher et a!.].979,1980, 1982, 1984, 1985, 1986) we have described the use of single or parallel opposed (POPAS) 300 MHz air cooled dielectric loaded microwave applicators. The purDose of this oape~ is to define the characteristics, mathematical rationale and the oenetration of EM energy of a triaDolicatnr system (TRIPAS) focused on a deep target in muscle phantom experiments. A mathematical model is

~resented based on synthesizing EM waves oroDagated in the biomedium, using its constitutive parameters, the incident energy and effective wavelength to predict and graBhica!Iv

demonstrate the convergent ’hot spot’ target within the concentric configuration of the three .apD!icators.

and to relocate the

MATERIALS AND METHODS Device Construction The TRIPAS system 2* is based on the use of three air cooled dielectric loaded applicators, 20x22 cm in aperture, which have been previous!y described (Bicher et al 1985). The system operates at 300 MHz, and is driven by fixed frequency generator capable of output of up to 1000 watts. The three applicators are mounted on a graduated circular stand (see Figure I) by the use of movable brackets. This allows the applicators to be placed in clos.e proximity to the skin overlying tne target area in a convergent fashion. The a~plicators are attached to brackets by universal ball joints, which allow angling to conform to the body surface.

In vitro Experiments

!n

vitr

o experiments were conducted by placing on the three sides of an equilateral triangular bu~t of plexiglass, measuring 41.5 c{ oer side.

cal points converging at the center of the

applicators

aperture fo

phantom box

The aPplica tors were placed flush against each side, with

triangle.

2 ~

Equipment SUDO!ied by HBC! Medical Group, Inc., 14427 Chase Street #203 manorama City, Ca 91402 USA

328

Figure I. TRIPAS Applicator Stand Construction of TRIPAS system. Note graded stand supporting 3 concentric relocatable air cooled horn applicators. For explanation see text.

329

The distance from the center of the triangle to the mid- point of each aperture was 12.5 cm. The ohantom was split in

a

plane peroendicular to one applicator, to allow placement

of

microthermocouDles and liquid crystal thermochromic paper

(~CP) between the aDp!:cators (see Figure 2). Changes in the

color of the thermochromic sheet indicated the thermal field and ~oint of wave convergence. Colors ranged from black (22 C~ throuQh red to b!ue (30 C), making heat field pattern clearly discernible. The comoosition of the muscle

eouivalent ohanzom material was that tabulated by

and Stuch!y (1980), having a dielectric constant of 50-58

F!m and conductivity of 0.909-0.952 S/m at 300 MHz.

Stuchly

SAR Determination

De~erminat

inv

ion of the power depositior pattern within the olved monitoring 27 precisely oositioned uDles in rectangular matrix on the LCP. The lit phantom was used to place sensoring devices al Diane, normal to one of the three radiating he LCP gave the additional advantage of an ure of the heat ~attern induced. The specific ate (SAR) from each sensor was determined using SAR = a!84"c* (A~/Xe ) W/kg [17,18], where c

phantom

microthermoco triangular sp in the centr apertures. T overall nict absorption r the formula:

~s the

s~ecific heat capacity of musc:e tissue phantom (0.86

cal/gm/deg.

normalized temperature (deg. C), and the volume was exposed to the microwave field was applied to the

prior to each reading. Peak temperatur e changes induced were

2.6 deg. C at 4cm depth, 0.7 deg C at at the summation point 12.5cm deep. exposure to the microwave field was re thermocontours simulated in FiQure 2.

CI,

T is the rise

in temoerature above t is the period of time

microwave energy.

phantom for 60 seconds

The

8cm depth, and 1.8 deg A longer duration of muired to Drovide the

Model Derivation

The complex propagation constan~ of medium is readily derivable from hyperbolic equations using Maxwell’s fundamental wave

EM energy in a wave (Helmholtz) equation ~

~ x ~ =( (/- + iw~ ) "~

2

÷or a stratified heterogeneous medium (single constant)

3 )

from Maxwell’s continuity law .-

propagation

330

5)

6)

APPLICATOR #3

Significantly Heated Areas

APPLICATOR #2

Figure 2. TRIPAS - Muscle Phantom Heating Pattern Positioning of the applicators for a typical measurement of temperature increment using thermochromic paper. Note the high intensity thermal field in front of each applicator, at the central convergent area and within a circle of positive interference surrounding it.

331

Eo.(5) specifies the wave equation while Eq.(6) specifies the complex ~ropagation constant. The general solution of E~.(5) for a homogeneous case is given :

"~y : Ae^(-(~z) + Re (~/z)

;

7)

for both forward and backward propagation on z-axis, where A and R are constants described by the medium and excitation characteristics. The complex propagation constant, Ea.(6), can be broken down into its real and imaginary parts :

whereo¢. (alpha) describes the attenuation factor, expressed in terms of the medium’s constitutive parameters :

= w~Z~/ 2) 1/2 [((I + (~-/g w) A 2) A 1/2

1)^1/2

9)

and where~ (beta) describes .the phase factor, expressed in terms of the medium’s constitutive parameters :

: w.~A&~12) "~ 112[((I + (,{I~ w)~2)~ 112 + 1)Al12]

10)

A harmonically excited,

traveling in a medium or media with known constitutive parameters can be described.

linearly polarized plane wave

~y : Er.e^{ -o~ z) e ^ i)wt-,~ z)

Thus precomputing Eq. (9) and Eo. (10)

I].)

respectively,Eo.

(11) can be easily computed and graphically simulated.

Plane Wave Interactive Simulation ~he prediction of the spatial heating effect on deep seated neoplastic tissue is mathematically tractable, and

can be deduced from E~.(11). !t is well established that a radiating source is most efficient when the physical parmeters of its aperture are comparable to the wavelength

Thus, the

wavelength

of

structure of the applicator and the source

the source being used (Guy et al. !974).

dictate in part, the distribution of an EM field profile. Studying the behavior of a plane wave in an excited medium with its characteristic complex propagation constant, does produce observable interaction of electromagnetic waves within KD the medium (Guy 1971), Kantor and Cetas 1977). The selection of these variables as shown by this simulation, depicts its potential value in Understanding electromagnetic interaction with biological media. This is further enhanced by the use of 3D graphical analysis. For an approximate linearly polarized plane wave, an axial E-field could be

written

Er:

332

(1/( ~r~, +

-I/(~ r)^2, + i/(~ r)^3 + !/(~" r)^n)e^( - ~r)

12)

where r is written

r

2

= ((x-x’)

+

in rectangular coordinate system :

(y-y’)

2

+ (z-z’))

2 1/2

and where n is an integer¯

2.6. TRIPAS

13)

Three applicators ar e configured around an encircled

eouilateral triangle to

’hot spot’ in order to

clinically desired area solution, Eo. (!I), fo propagated in the medium The rationale behind the from the theory of wire

target and relocate the calculated

achieve significant heating in the

¯ Simulation of the analytical

r the plane electromagnetic wave is then implemented. design of TRIPAS is not different antennae. Applicator apertures are

considered as planar co llections of small electric ( or

magnetic) dipoles, each o waveforms as the source individually. A monotone biomedium ~lane by convolut solutions on a surface expre

Ey = Er. e~(-c~ Ix^2 + ~?-))~ .cos(6.238(#^2 + y^2)^1

f which radiates complex energy to impinge on the tissue excitation is modelled in the ing ( superimposing) olane wave ssions :

1/2.e^( -

/2/ )

(x^2 + #A2) 1/2) ].a)

(see notation for definition It is presupposed that

parameter). small electric (or magnetic)

dipoles radiate complex e nergy waveforms, the energy

contributions of which are s patially superimposed and summed

ns at the point where they meet ase, while negating each other

over individual contributio in the biomedium when in ph when out of phase.

TRIPAS Analysis

Assumptions

1) A convergent linearly polarized beam axially propagates

on the

source.

positive z-axis from a

strategically located

2)

Each beam simulates the characteristic excitation and

the

medium’s complex propagation constant.

3)

Heterogeneous layers are stratified to homogeneous

layers to enhance oaractical single oarametric values for the medium dielectric constant and conductivity.

4) Each applicator is designed for 300 MHz, EM energy absorption is enhanced by electrical dipoles characteristics in Rayleigh region ( Kritikos et al. 1976 (~R < 2D~F1)).

5)

A muscle phantom with dimensions consistent with the

effective wavelength of 300 MHz is selected to enhance

constructive interference. P. et al 1985.

(This is derived from Nilsson,

333

Figure 3 shows the simplified analytical geometry which illustrates the convergence of the beams from three dipoles on the vertices of an equilateral triangle. The point of maximum summation, or the point of minimum substration, is located at the center of an encircled equilateral triangle resulting from the three tangential dipoles (Figure 3, case 1). Assuming the point of convergence as the aperture focal point (R) in the medium, R is selected to be proportional to the effective wavelength of the medium to meet Rayleigh region such as:

Target Relocation

The relocation of the target ’hot spot’ is postulated by angular tilting of two adjacent apertures so as to display a constructive focal point within the quadrants of the circle. Figure 3, cases 2 to 4, display theoretical results of tilting a pair of adjacent applicators. The tilting angle of the pair of adjacent applicators can be derived from simple

geometrical

analysis:

~ ( theta ) = arcsin ( L/R - 1)

16)

where L is the distance from the third aperture to the

perpendicular line of adjacent tilted applicators. In other words knowing the precise depth of a tumor in a strategical oreconfiguration of TRIPAS, a constructive interference is postulated to give differential heating effect resulting in the formation of a ’hot spot. In order to demonstrate the

feasibility of this postulation, 3D graphic

simulations

and thermographic split muscle phantom experiments were

implemented as previously described (see 2.1 -2.3).

Graphic Analyses

For computer simulation of dipoles plane wave, Eq (14), three element sources were located 120 degrees apart around a rectangular co-ordinated circle with its center as the origin ( Figure 3, case 1) Two commercial 3D graphics packages (3*, 4*) were invoked to implement the computer simulation. A fortran 77 routine was written on main-frame to a priori compute the and valves, with the medium’s constitutive parameters: relative permittivity, conductivity and the excitation frequency. These were passed into the 3D Curve package to generate a

data file. The flexible Golden Surfer package was invoked to produce the 3D output response of the simulations. Selection

of the co

ordinate system can be obtained from :

(O,r), (r,-rsin30), (-r, -rsin30)

17)

3* Curve Three

Suite 308~.San Diego CA 92117 4* Surfer Golden Software Inc., 80i I~ Street, P.O.Box 281 Golden CO. 80402

D West Coast Consultants, a202 Genesee Ave,

334

Basic Dipoles Configuration

Case 1

Case

Case 3

Case 4

Figure 3. TRIPAS Analysis - Postulated Target Relocation Arrows indicate dipoles strategically located around encircled equilateral triangle. Case l: Dipoles sum their plane - wave contributions at the center.

Case 2:

points by theta to enhance relocation of

point (target) at the RHS of circular segment. Case 3. Pair dipoles rotated at their tangential mid - point by theta to enhance relocation of summation point (target) at the Bottom circular segment. Case 4. Pair dipoles rotated at their tangential mid - points by theta to enhance relocation of summation point (target) at the LHS circular segment.

Pair dipoles rotated at their tangential mid -

summation

335

Three ~i~oles circularly located at the above rectanQular co- ordinates with center {0,0). The valve (r) is matched to (R), the axial focal length, though (r) can be arbitrariTy selected. Each co ordinate goes into Eq. 4, respectively :

~y : Er.e (-~c (x+12.5)~2

+ (y~5.3)^2)~1/2)

^

.e (-/~ ((x+12.5)^2

+ (v-_6.3)^2) 1/2)

.cos(6.283 (x+12;5)^2 + (y-6.3)^1/2~Y~)

~y : Er.e (-~ ((x-12.5)^2 -+ (~v~-6.3)~I/2)

.cos(6.283(ie (~.5((x-12 5)- 2 ~+ (y-6.3)^2)^1/2)

x-1 )~’2 + iy-6.3) 2) 1/2~e(~)

18c)

for r = R = 12.5 Creating the plane wave superimposed on the traveling surface wave ( see Figure 3a and Figure 5 )

Results SAR measurement

The results of the SAR measurements indicate that the temperature increases obtained were greatest close to each

radiating aperture, and then lessened substantially, until a zone of summation is reached, where they create a ’hot

spot’

closely approached those measured at the near field of the

aperture (see Figure ~).

Phantom Temperature Determination

The SAR measurements at the 12.5 cm ’hot spot’

Thermal responses visualized on the liquid crysta! sheets showed three different zones of preferential heating :A ’hot spot’ was located close to #ach applicator. A second clearly defined heat zone appeared at the center of the phantom, at the point of beam interaction. Both of these zones are about 6 cm in diameter. A third heat zone is circumferential about midway between the peripheral and central hot spot ( see Figure 2), about 3.~ cm wide ( one Quarter of the effective wavelength of 13.4 cm at 300 MHz in the muscle Phantom).

Simulation

The results of the simulation of EQs. 18a - c

are

disolayed 3-dimensionally in Figure 5. The inputs

for

computing the complex propagation constant and

its

components (~,~) simulated in the muscle tissue excited at

336

SUMMARY RESULTS 11/19/86 PM 12.5 cm (TRIPAS) PI’LANTOM 60 Second Time 600 WATTS Power

ANTENNA #I

TENNA #2

85

73

38

 

"

~ 9cm 2~8

=

~

 

_

109

84

ANTENNA #3

SAR TRIPAS 600 WATTS (I MINUTE)

Figure 4. TRIPAS - SAR Profiles

SAR

(specific absorption ratio) measured in

a triangular

muscle

phantom,

using

300 MHz

at

600

Watts

equally

split

among

three

equivalent

(dimension,design) for 60 seconds.

SAR’s

applicators in the area

of summation approximate those near the

eo~licator aDeratures.

front of the

337

300 MHz, were : permittivity value of 54 F/m and conductivity value of 1.07 S/m, with free space permeability value of !2.57x10 H/m and the permittivity of free space as 8.854xi0 F/m. These parameters were apDropiately scaled as input variables into the graphic package for the data file.

The

calculated theoretically, but in this case was extrapolated from the muscle ohantom heating pattern studies. A typical value of ~eff= 13.a cm was used ( see SAR measurements ).

selection of effective wavelength (~eff) can

be

The dispersive effect of the plane wave was accomplished

by

the addition of electromagnetic plane wave solution with

surface expression ( see

displays the 3D output surf ace plot of the simulation. The

letter marker A,B and C i ndicate the origin of the diooles

120 degree separation in circular

, strategically located at configuration. The arrow

Eas.(14) and (15)). Figure 5

marker points to

the central

summation ’ hot spot’. The main features highliahted by

these 3D plots are : 1) high intensity singularity in front of each simulated aperture, 2) rapid decay in amplitude intensity due to generation of destructive interference from subtractive surface waveforms, 3) at even greater depth a second high intensity area due to additive interference causina a peaking standing wave, 4) followed by subtractive interference creating an intensity valley and 5) finally producing the theoretically predicted summation at the

centrally located ’ hot spot’

the aPerture (source) is a common observation in experimental and theoretical modellings (Bach Andersen 1984, Gee et al .1984, Kantor and Cetas 1977), that accounts for near- field effects. The surface dispersive effect is predominant at the viewing angle in this simulation. The amplitude steering (modulation) of the target ’hot spot’ is

implemented by the inclusive term E Eqs. 18a-c. It should be noted that the above surface plot is in very good agreement

The high intensity peak at

with

experimental observations as

described

earlier,

(comparing Figures 2 and 5). Note, this specifically applied

to

postulation.

case i of Figure 3 relating to the

Discussion

theoretical

The present results make use of a mathematical model of

radiating dipoles to predict the coherent and noncoherent

interference

wave

sources interacting within biological media to produce a relocatable ’hot s~ot’ The muscle-~hantom experimental results in part verified this postulation.

of three converging electromagnetic

Previous studies (Bach Andersen 1984,Turner and Kumar

1982,

Wait 1986),solved domain-integral equations for

electric field vector ~otential as a result of induced magnetic current elements derived from fundamental Maxwell’s

classic microscopic equations,

Turner and Kumar

(1982,’84) used Huygen’s principle to simulate a horn-tyoe apolicator as an array of point-source dipole radiators, in order to predict the heating patterns and ~erformance of the

provided versatility of

implementing the medium heterogeneity.

338

Figure 5. TRIPAS - Simulatien

3D surface plot displaying pattern of split 300MHz microwave beams into muscle phantom. Note:l) the area of central converaence indicated by arrow(as postulated in Fig. 3 case I), ~) high intensity thermal field in front of each applicator (A,B, and C) and 3) circular area of positive interference at approximate I/8 wavelength depth between the applicator and the convergent center.

339

aperture. Such mathematical model was limited in its ability to soatial!y predict the interaction of harmonically excited plane waves in biological medium. Johnson et al. (1984,’85) and Sato (1986) analyzed circular compact arrays simulating resonance conducting p~ates as magnetic current sources. A mathematical integration over the aperture surface yields field distribution. This computational method is limited by the convergence or divergence of the numerical technioue used for the integration.

Bach Andersen (1984] modelled an array of dipoles to

explicitly define radiative antenna gain for oower density at a given ~oint relative to the total input Dower. This concept was used to analyze radiative apertures and their penetration capability in biological tissue. This author

(Bach

Andersen

1984) further showed the

theoretical

synthesis of one- dimensional convergent beams meeting at a focal ooint to produce constructive interference. He

p~ctorially

demonstrated that two waves traveling in

oDoosite directions produce either an additive coherence or

subtractive noncoherence effect. The present investigation

followed the same theoretica

I

postulation.

For cylindrical geometry the larQe number of waves add to produce power intensity convergence at the axis (Lin 1982).

This central cylindrical ~ocusing is oenerally applied in

regional heating of cylindrical tissue, (Samu!ski et al., 1987 and Turner 1984), but lacks the flexibility to relocate a localized ’hot spot

Nilsson et al. (1985) tilted two applicators at 45 degrees. They reported a distinct heatin~ pattern when both the radiative source had no phase relationship, while constructive and destructive interference were observed when both app!icators were excited in Phase coherently.

Gee et al. (1984), Bach Andersen (1984) and Ling et al (1984) Presented theoretical and experimental models of near

~eld ~hased array focusing analyzed in 3D plane wave

profiles. The alternative use of an interactive Diane waves model might ease the limitations inherent in the above simulation techniques.

Earlier, we ~e~orted (Bicher et al 1985) an experimental

parallel

opposed

s~stem

that

achieved

therapeutic

temperatures in the 42 to 43 degree Celsius range at 8 cm

depth in both muscle e~uivalent phantom and in pigs 20-30

cm thicK. !n other papers (Bicher et al 1982,

defined the clinically usable penetration using one air coo~ed applicator operated at 300 MHz to be 5 cm. Usinm POPAS (two o~oosed applicators operated in phase), we were able to heat theroeutically to a depth of 8 cm. By olacinm

one

treatment of tumors at moderate depth, in thorax, abdomen and pelvis, have proved successful.

Our results of in vitro experiments and mathematica I simulation ( Figure 3, case i) clearly show effective heatinQ at a depth of 12.5 cm using 3 convergin~ microwave

84, ’86) we

aDolicator anteriorly and the other

posteriorly,

340

beams from standard 300 MHz external applicators. The

flexibility of the system (TRIPAS) and the ability to change the incident angle of the beams to relocate the ’ hot spot’

extremely

practical for the treatment of deep seated tumors, without the need to heat an entire body region as is required with

current phased array systems which operate at freauencies. P~sitioning of the air gap applicators

within the target volume,

make the system

lower

around

the patient is quick and easily reproducible. aDolicators have poor coupling however, so there is some These energy loss. ~n the present system this is compensated by the use of a high power generator operating at fixed freouency (300 MHz), capable of 300 watts per applicator. Thus a 900 watts generator for TRIPAS wi!l be required for clinical use. Such a device has already been built and is operational in our laboratory.

The good correlation between our mathematical predictions and phantom studies validates the theoretical approach used. The ability of the TRIPAS system to predict the location of the ’hot spot’ within the treatment field makes computer ~lannina o~ the applicators ~ositionino in the clinical situation feasible.

Nomenclature D = aD~licator aperture dimension (cm) Er = axial spatial electric field magnitude (v/cm)

Ey : electric field complex vector (v/cm) f = frequency (MHz)

= magnetic field omplex vector (A/cm)

= imaginary operator (Sq.root (-1))

= numerical approximate integer for axial E -

= distance from the aperture to target - tumor

= axial aperture focal length (cm) : graphical radius x,y,z = rectangular coordinate system

= 2’~f ; angu!art frenquency Irad)

= attenuation factor (Np/m)

field

(cm)

= phase factor (rad/m)

=conductivity of the medium (S/m)

= relative dielectric constant

./~ = free space ~ermeabiliti (H/m)= complex ~ropagation constant (H.Np/m) eff = effective wavelength (cm/ cycle)

(theta) = tilting axial aperture angle (deg)

= vector differential operator ~= laplace o~erator = variable incrememt

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